T cell receptor repertoire of T cells in the kidneys of patients with lupus nephritis.

Abstract

To determine the role of T cells in the pathogenesis of lupus nephritis (LN). Renal biopsy specimens from 12 patients with systemic lupus erythematosus were used for the experiments. We analyzed T cell receptor (TCR) Vbeta1-20 family genes on intrarenal T cells and on peripheral blood lymphocytes (PBLs) by nested reverse transcriptase-polymerase chain reaction (PCR) and Southern blot analysis. Nucleotide sequence was determined in the third complementarity-determining region of the TCR Vbeta gene in expanded T cells. Messenger RNA (mRNA) expression levels of Th1 and Th2 cytokines on infiltrating T cells were measured by nested PCR. The repertoire of TCR Vbeta in intrarenal T cells was relatively restricted compared with that in PBLs. The TCR Vbeta8 and TCR Vbeta20 genes were preferentially expressed in 6 of 12 patients (50%) and the TCR Vbeta9 and TCR Vbeta14 genes were expressed in 5 of 12 patients (42%). Junctional sequences of complementary DNA encoding the TCR Vbeta8 and TCR Vbeta20 genes in intrarenal T cells showed oligoclonal expansion, indicating antigen-driven stimulation. Interleukin-4 (IL-4) and IL-10 mRNA were highly expressed on intrarenal T cells, while interferon-gamma mRNA was not detected. Our findings suggest that T cells infiltrating the kidneys of patients with LN may recognize restricted epitopes on antigens and function as Th2-type T cells.